While data from several empirical studies support the idea that smokers process cigarette-related stimuli as motivationally relevant, very few studies have investigated if smokers exhibit reduced sensitivity to natural rewards (i.e., intrinsically pleasant stimuli). Obtaining this knowledge will allow for the implementation of new interventions aimed at enhancing the saliency value of natural rewards, an approach that might increase smoking abstinence. The long-term goal of our research group is to understand the neurophysiologic mechanisms underlying relapse and to improve smoking-cessation interventions. The objective of this proposal is to determine the role of sensitivity to intrinsicaly rewarding (i.e., pleasant) stimuli in the maintenance of smoking addiction. Our central hypothesis is that smokers with reduced sensitivity to intrinsically pleasant stimuli will have mor difficulty quitting smoking and achieving long-term abstinence. This hypothesis was developed thanks to preliminary data collected in our laboratory using event-related potentials (ERPs), a direct measure of neural activity. The rationale for the proposed research is that once we can identify smokers who exhibit reduced sensitivity to intrinsically pleasant stimuli, specific interventions to normalize the reactivity of the brain reward system can be implemented for these individuals. Such individualized interventions (either pharmacological or psychological) will increase long term smoking cessation rates with a significant positive impact on human health. We will test this hypothesis by pursuing three specific aims: 1) Determine the role of nicotine addiction in altering sensitivity to intrinsically pleasant stimuli; 2) Identify the role hat sensitivity to intrinsically pleasant stimuli has on influencing smoking abstinence during a smoking cessation attempt; 3) Build and validate a long-term smoking abstinence predictive model to improve personalized treatment for smoking cessation. This approach is innovative because, by using ERPs to directly measure brain activity evoked by intrinsically emotional stimuli, we will be able to evaluate the role that individual differences in the brain reward syste have in influencing one's ability to quit smoking. The proposed research is significant because it will fundamentally advance our knowledge of the neurobiological processes involved in drug addiction. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because determining if smokers lose sensitivity for intrinsically rewarding stimuli is the necessary preliminary step to developing new treatments aimed at restoring the saliency value of natural reinforcers and significantly increasing the long-term success of smoking cessation interventions. Hence, the project is relevant to the NIDA Clinical Neuroscience Branch's mission of characterizing how abused drugs affect the function of the human central nervous system and understanding the role of individual differences underlying the maintenance of drug addiction.